Retrovectors are widely used for gene transfer in gene therapy, tissue culture and transgenic animals for research or commercial applications.. A long recognized limitation of current retrovectors is that introns are spliced out as retrovector particles are made in packaging cells. Introns may regulate the expression of the genes and convey tissue specificity. The presence of introns boosts expression as a consequence of active splicing. This proposal tests the design of retrovectors which preserve introns by utilizing elements of viral RNA export mechanisms naturally occurring in the complex retroviruses. A packaging cell expressing an RNA export enabling protein (Rex) will be used to produce vectors whose constructs contain the corresponding Rex responsive element (RxRE). In combination this should allow the making of retroviral vectors which contain introns. These vectors subsequently allow the transfer of introncontaining constructs into the final host cell. Relevance: Previously considered "junk DMA", introns are now understood to exert significant effects on the adjacent coding regions of genes. By enabling the transfer of intron-containing genes we anticipate (a) providing a means to make gene therapy vectors with greater predictability of expression and tissue specificity; (b) providing a boost to protein expression in cell culture bioreactor systems and transgenic animals and (c) providing a useful research tool to enhance understanding of RNA biology.